Distribution of Antioxidant Enzymes in Developing Human Lung, Respiratory Distress Syndrome, and Bronchopulmonary Dysplasia

Kaarteenaho‐Wiik, Riitta; Kinnula, Vuokko L.

doi:10.1369/jhc.4a6291.2004

Cited by 36 publications

(22 citation statements)

References 54 publications

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“…Catalase was not detected in alveolar tissue even in the nonsmokers (data not shown). This is consistent with findings by KAARTEENAHO-WIIK and KINNULA [10], showing immunoreactivity of catalase in bronchiolar epithelium in human lungs. However, despite minimal change in bronchiolar catalase in smokers without COPD, a dramatic decrease in catalase staining in the cells of the terminal bronchioles was detected in smokers with COPD ( fig.…”

Section: Characteristics Of Human Subjectssupporting

confidence: 93%

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Bronchiolar epithelial catalase is diminished in smokers with mild COPD

et al. 2012

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This study aimed to investigate bronchiolar catalase expression and its relationship with smoking and/or chronic obstructive pulmonary disease (COPD) in humans and to determine the dynamic change of bronchiolar catalase expression in response to cigarette smoke in mice.Lung tissue was obtained from 36 subjects undergoing surgery for peripheral tumours, consisting of lifelong nonsmokers and smokers with or without COPD. Male C57BL/6 mice were subjected to cigarette smoke exposure for up to 3 months followed by a 28-day cessation period. We quantified bronchiolar catalase mRNA using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction. C22 club cells (Clara cells) in culture were exposed to cigarette smoke extract and monitored for viability when catalase expression was decreased by siRNA.Catalase was decreased at mRNA and protein levels in bronchiolar epithelium in smokers with COPD. In mice, bronchiolar catalase is temporarily upregulated at 1 day after cigarette smoke exposure but is downregulated by repeated cigarette smoke exposure, and is not restored long after withdrawal once emphysema is developed. Decreasing catalase expression in C22 cells resulted in greater cigarette smoke extract-induced cell death.Bronchiolar catalase reduction is associated with COPD. Regulation of catalase depends on the duration of cigarette smoke exposure, and plays a critical role for protection against cigarette smoke-induced cell damage. @ERSpublications Regulation of bronchiolar catalase in COPD depends on the duration of cigarette smoke exposure

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Section: Characteristics Of Human Subjectssupporting

confidence: 93%

“…Catalase is expressed during the later stages of lung development, and is constitutively expressed in airway and alveolar epithelial cells and in macrophages in adults [10]. To date, several studies have focused on catalase in pathological lung status [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Bronchiolar epithelial catalase is diminished in smokers with mild COPD

et al. 2012

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“…However, other potential regulatory mechanisms warrant investigation. Prior studies in the developing human lung (17-wk gestation) indicated that SOD2 expression is limited to the alveolar and bronchial epithelium as well as macrophages (13). However, our immunohistochemical data indicate that in the postnatal lamb lung, there is robust expression of SOD2 in both the endothelium and the smooth muscle layers of pulmonary arteries.…”

Section: Discussioncontrasting

confidence: 60%

Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow

Sharma

Grobe

Wiseman

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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SM. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow. Am J Physiol Lung Cell Mol Physiol 293: L960-L971, 2007. First published July 13, 2007; doi:10.1152/ajplung.00449.2006.-Increasing data suggest that oxidative stress, due to an increased production of reactive oxygen species and/or a decrease in antioxidants, is involved in the pathophysiology of pulmonary hypertension. Several antioxidant systems regulate the presence of oxidant species in vivo, and of primary interest are the superoxide dismutases (SOD) and catalase. However, little is known about the expression of antioxidant enzymes during the development of pulmonary hypertension. This study uses our lamb model of increased postnatal pulmonary blood flow, secondary to in utero aortopulmonary graft placement (shunt lambs), to investigate the expression patterns as well as activities of antioxidant enzymes during the early development of pulmonary hypertension. Protein levels of catalase, SOD1, SOD2, and SOD3 were evaluated by Western blot, and the activities of catalase and SOD were also quantified. In control lambs, protein expression and activities of catalase and SOD2 increased postnatally (P Ͻ 0.05). However, SOD1 and SOD3 protein levels did not change. In shunt lambs, catalase, SOD1, and SOD2 protein levels all increased over the first 8 wk of life (P Ͻ 0.05). However, SOD3 did not change. This was associated with an increase in the activities of catalase and SOD2 (P Ͻ 0.05). Compared with control lambs, catalase and SOD2 protein levels were decreased in 2-wk-old shunt lambs and this was associated with increased levels of hydrogen peroxide (H 2O2) and superoxide (P Ͻ 0.05). Developmentally superoxide but not H 2O2 levels significantly increased in both shunt and control lambs with levels being significantly higher in shunt compared with control lambs at 2 and 4 but not 8 wk. These data suggest that the antioxidant enzyme systems are dynamically regulated postnatally, and this regulation is altered during the development of pulmonary hypertension secondary to increased pulmonary blood flow. An increased understanding of these alterations may have important therapeutic implications for the treatment of pulmonary hypertension secondary to increased pulmonary blood flow.catalase; superoxide dismutase; congenital heart disease OXIDATIVE STRESS AND the increased production of reactive oxygen species (ROS) have been implicated in the development of both pulmonary and systemic vascular disorders (10,(23)(24)(25)27). Oxidative stress is characterized by an increase in the production of oxidant species [superoxide, hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), peroxynitrite] or a decrease in the antioxidant capacity of the cell/organism by affecting levels of antioxidants or antioxidant enzymes. Although the altered production of ROS has been the focus of much investigation, less is known about alterations in the antioxidant enzymes.Antioxidant enzyme systems play a critical role in the regulation of oxidant levels ...

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“…eNOS is then said to be uncoupled. Under these conditions, superoxide is quickly converted into peroxynitrite if NO is also present locally, or into H 2 O 2 via superoxide dismutase (SOD) (22). H 2 O 2 is converted into H 2 O and O 2 by catalase and glutathione peroxidase (9).…”

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confidence: 99%

Age-dependent endothelial nitric oxide synthase uncoupling in pulmonary arteries of endoglin heterozygous mice

Belik

Jerkić

McIntyre³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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, and clinical signs of disease are generally more evident later in life. We previously showed that systemic vessels of adult Eng heterozygous (Eng ϩ/Ϫ ) mice exhibit increased vasorelaxation due to uncoupling of endothelial nitric oxide synthase (eNOS). We postulated that these changes may develop with age and evaluated pulmonary arteries from newborn and adult Eng ϩ/Ϫ mice for eNOS-dependent, acetylcholine (ACh-induced) vasorelaxation, compared with that of age-matched littermate controls. While ACh-induced vasorelaxation was similar in all newborn mice, it was significantly increased in the adult Eng ϩ/Ϫ vs. control vessels. The vasodilatory responses were inhibited by L-NAME suggesting eNOS dependence. eNOS uncoupling was observed in lung tissues of adult, but not newborn, heterozygous mice and was associated with increased production of reactive O2 species (ROS) in adult Eng ϩ/Ϫ vs. control lungs. Interestingly, ROS generation was higher in adult than newborn mice and so were the levels of NADPH oxidase 4 and SOD 1, 2, 3 isoforms. However, enzyme protein levels and NADPH activity were normal in adult Eng ϩ/Ϫ lungs indicating that the developmental maturation of ROS generation and scavenging cannot account for the increased vasodilatation observed in adult Eng ϩ/Ϫ mice. Our data suggest that eNOS-dependent H2O2 generation in Eng ϩ/Ϫ lungs accounts for the heightened pulmonary vasorelaxation. To the extent that these mice mimic human HHT1, age-associated pulmonary vascular eNOS uncoupling may explain the late childhood and adult onset of clinical lung manifestations. lung; newborn; pulmonary vascular resistance; hereditary hemorrhagic telangiectasia LUNG BLOOD FLOW IS MOSTLY dependent on the regional arteriolar and venular intraluminal diameter that ultimately determines the pulmonary vascular resistance (PVR). Nitric oxide (NO) is constitutively produced by endothelial and smooth muscle cells (39) via synthases (NOS) of which there are three isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Although there is evidence that iNOS and nNOS are expressed in the fetal pulmonary vasculature (38), lung eNOS protein expression increases during gestation suggesting that its vascular tissue content and/or activity is in part responsible for the high PVR prenatally and the changes occurring after birth (15). In sheep, lung eNOS expression is maximal in late gestation (34), whereas in rats it is highest either before (33), or immediately after, birth (23). Postnatally, lung vascular tissue eNOS expression was shown to decrease with age in pigs (17).eNOS converts L-arginine to L-citrulline to generate NO. Its activity is dependent on Ca 2ϩ /calmodulin (CaM), but also on subcellular localization, posttranslational modifications, and interaction with several regulatory proteins, including Hsp90 (11,14). Hsp90 facilitates CaM-induced release from caveolae and acts as a scaffold factor for eNOS; it is necessary for eNOS phosphorylation at Ser1177 (13, 43). This complex process controls the state of eNOS ac...

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Distribution of Antioxidant Enzymes in Developing Human Lung, Respiratory Distress Syndrome, and Bronchopulmonary Dysplasia

Cited by 36 publications

References 54 publications

Bronchiolar epithelial catalase is diminished in smokers with mild COPD

Bronchiolar epithelial catalase is diminished in smokers with mild COPD

Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow

Age-dependent endothelial nitric oxide synthase uncoupling in pulmonary arteries of endoglin heterozygous mice

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